Abstract
Background
Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA).
Aims
We hypothesized that a genome-wide analysis of blood gene expression could offer new
prognostic tools and lines of research.
Methods
Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583
that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected
in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation.
Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes).
Patients were classified into two categories representing neurological favorable outcome
(cerebral performance category [CPC] = 1-2) vs unfavorable outcome (CPC > 2) at Day 60 after OHCA. Differential and functional enrichment
analyses were performed to compare transcriptomic profiles between these two categories.
Results
Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively.
Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect
the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts
differed at Day-0 between patients with unfavorable vs favorable neurological outcome.
This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed
a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity
and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family
was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation
were observed. Up-stream regulators analysis showed the implication of numerous factors
involved in cell cycle and damages. A logistic regression including a set of genes
allowed a reliable prediction of the clinical outcomes (specificity = 88%; Hit Rate = 83%).
Conclusions
A transcriptomic signature involving a counterbalance between adaptive and innate
immune responses is able to predict neurological outcome very early after hospital
admission after OHCA. This deserves confirmation in a larger population.
Keywords
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Article info
Publication history
Published online: March 15, 2019
Accepted:
March 10,
2019
Received in revised form:
February 27,
2019
Received:
December 19,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
